Meta-phenoxybenzoic acid and its lower alkyl esters are the simplest representatives of a group of compounds that differ by the substituents on either of the two benzene moities. Some of these chemicals have been noted for their herbicide properties, others are used as intermediates in preparing commercially important herbicides.
The reaction between the alkali metal salt of phenol or a substituted phenol and the m-halobenzoic lower alkyl ester or substituted ones has been used in most of the syntheses. This general reaction is known as the Ullmann ether synthesis as it was reported first by Ullman and Sponagel, Ber. Deut. Chem. Ges., 38 2211 (1905).
Only two references were found, however, that refer to the particular preparation of the methyl m-phenoxybenzoate by the Ullmann Syntheses: J. Pharm. Soc. Japan, 74, 1061 (1954) and J. Pharm. Soc. Japan, 74, 1728 (1954). In both of them, the m-bromo analog is used in the presence of a catalyst consisting of copper and cupric acetate. In both cases, the reported yields were rather low, namely 39 and 22 percent, respectively.
It is, accordingly, the main objective of the present invention to provide a process for the preparation of m-phenoxybenzoic acid or its lower alkyl esters or substituted derivatives thereby by the Ullmann reaction, but in the presence of a catalyst that will provide the reaction under milder conditions and higher yields.
Other objectives of the invention will be apparent to those skilled in the art from the present description.
In the course of the research which resulted in the process of the present invention, the reaction of methyl m-chlorobenzoate and sodium phenate was used at first in the screening of the possible catalyst candidates. It was surprising that better results were obtained in carrying the reaction without any catalyst, than when using the copper salt catalysts disclosed in the abovementioned references.
It was soon recognized that the greatest obstacle to good yields was the concurrent saponification of the starting material, yielding anisole instead of the desired ether. A transesterification of the methyl ester with the phenate is another side reaction. A variety of copper, as well as non-copper catalysts, was tried. It was discovered that copper sulfate was the only catalyst which provided distinctly superior yields.